Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, with almost 90% of these people being in developing countries. Epilepsy is more likely to occur in young children or people over the age of 65 years; however, it can occur at any age. Epilepsy is usually controlled, but not cured, with pharmacotherapy, although surgery may be indicated in exceptional cases. Despite the reliance on pharmacotherapy as the primary approach in controlling the disease, over 30% of people with epilepsy do not have seizure control even with the best available medications. Not all epilepsy syndromes are life-long; some forms are confined to particular stages of childhood. Epilepsy should not be understood as a single disorder, but rather as a group of syndromes with vastly divergent symptoms, but all involving episodic abnormal electrical activity in the brain.
In addition to its approved use in the treatment of individuals suffering from epilepsy, phenyloin has been used clinically as an antiarrhythmic agent, an agent to treat preeclampsia, and an agent to treat trigeminal neuralgia. Pharmacokinetically, however, phenyloin exhibits a rate and extent of absorption that can vary widely and is metabolized greatly in the liver. Thus, although phenyloin possesses unique pharmacological properties, the ability to safely and efficaciously utilize the drug for other indications is believed to have been hampered by the drug's wide pharmacokinetic variations following administration.
Therefore, pharmacotherapy with hydantoins, such as phenyloin, could be improved if compounds that retained some degree of the pharmacology of these drugs, yet possessed different chemical structures that could result in different pharmacokinetic profiles. As a consequence, there is an unmet need for developing novel hydantoin compounds.
The present invention seeks to address these and other needs in the art.